Method of producing sulfanilylthioureas



Patented Apr. 3, 1951 METHOD or PROI'JUCING'SULFANILYL- .ZEHIOUREASBruce Earle Baker, 'Stanbridge East, Leo Brick man, Montreal, and LeoEdward Ryan, Dorval, Quebec, Canada, assignors to Monsanto ChemicalCompany, St. Louis, M9,, a corporation of Delaware No Drawing.Application June 24, 1946, Serial No. 678,884. In Canada November 29,1944 Section 1, Public Law 690, August 8, 1940 latentexpires November29, 1964 2 Claims. (Cl. 260-7397.?)

This invention relates to the production of acetylsulfanilylthiourea andsulfanilylthiourea and is directed to a new and improved method wherebythey may be produced more readily and economically.

Sulfanilylthiourea shows promise of being of value in combatingbacterial infections while acetylsulfanilylthiourea is a valuableintermediate in the production of sulfathiazole, which, as is wellknown, is an antibacterial agent of outstanding merit. It is desirabletherefore, that a process be developed for producing them on acommercial scale.

According to the present invention, we have found thatacetylsulfanilylthiourea and sulfanilylthiourea can be readily obtainedby the reaction of the calcium salt of acetylsulfanilylcyanamide withhydrogen sulfide to give acetylsulfanilylthiourea, which is thenhydrolyzed to sulfanilylthiourea. The reaction may be representedschematically as follows.

011,0 ONHCelEhSOzNHCN HzS Acetylsulfanilylcyanamide c1130 NHC6H4SOzNHCSNHz Acetylsullanilylthiourea hydrolysis NH2C6H4802NHOSNH2Sulfanilylthiourea In carrying out the process of the present inventiona sulfanilyleyanamide of general formula RNHCaHiSOaNCN where R=acyl or HR =calcium usually in the form of a salt, is reacted with hydrogensulfide in aqueous solution in a sealed tube. The temperatures employedrange from 70 to 160 C. The water may be replaced in Whole or in part byother hydroxylic solvents such as ethanol or methanol. The time of thereaction varies with the pressure and the tem perature used. Pressuresup to several hundred pounds per square inch are preferred to hasten thereaction. The pH of the reaction medium should be between the limits of4 to 11, preferably 7-10 where best yields are obtained.

The hydrogen sulfide may be provided by ammonium sulfide, sodiumbisulfide or the like salts which dissociate at the temperature of thereaction or it may be generated in situ.

When acetylsulfanilylcyanamide is used acetylsulfanilylthiourea isformed. The acetylsulfanilylthiourea can be readily converted intosulfanilylthiourea. by any one of the methods of hydrolysis well knownto the art. When sulfanilylcyanamide is reacted with hydrogen sulfide atelevated temperatures and pressures, sulfanilylthiourea is obtaineddirectly.

The following specific examples are illustrative of the preferred methodof carrying out the reaction but are not intended to limit the scope ofthe invention.

EXANEPLE I Preparation of ocetylsulfam'lylthzourea Two hundred andtwenty-five grams of calcium acetylsulfanilylcyanamide suspended in 1500ml. water were placed in a steel autoclave fitted with an agitator,thermometer well, and an inlet tube for hydrogen sulfide gas. Themixture was heated to 100 C. for 16 hours with constant agitation,during which time hydrogen sulfide gas was passed into the mixture sothat the pressure was kept constant at pounds.

,At the end of this period, the pressure was re- Preparation ofsulfanilylthiourea by deacetylation Ten grams ofacetylsulfanilylthiourea was refluxed for ten minutes with 40 ml. of 10%sodium hydroxide solution. The solution was now cooled and acidifiedwith hydrochloric acid until the solution turned Congo paper blue. Thesulfanilylthiourea precipitated out and was filtered off and washed withwater. It weighed 6 g.

, It is obvious that the above examples may be varied or modifiedwithout departing from the spirit of the invention.

We claim:

1. In a process for the preparation of sulfanilylthioureas andderivatives, the steps comprising heating an aqueous suspension ofcalcium acetyl sulfanilylcyanamide at a temperature of at least C. withhydrogen sulfide under pressure, and thereafter dissolving sodium 3chloride into the aqueous reaction mixture and REFERENCES CITEDcrystallizmg out the Sodium Salt of acetyl The following references areof record in the ianilylthiourea from the aqueous reaction mixfile ofthis patent:

ure. I

2. In a process for the preparation of sulfa- 5 UNITED STATES PATENTSnilylthioureas an derivatives, the steps compris- Number Name Date ingheating an aqueous suspension of calcium 2,254,136 Buck et a1 Aug. 26,1941 acetyl sulfaniiylcyanamide at temperatures 2,336,907 Winnek Dec.14, 1943 within the range of 70 to 160 C. with hydrogen 2,380,006 Winneket a1 July 10, 1945 sulfide under pressure, and. thereafter forming 10and separating the sodium salt of acetyl sul- FOREIGN PATENTSfanilylthiourea by dissolving sodium chloride u er Country Date into thehot aqueous reaction mixture and then 260,061 Germany May 13, 1913cooling the aqueous reaction mixture to crystal- 297,999 Great BritainOct. 4, 1928 lize out the sodium salt of acetyl sulfanilyl- 15 336,111Great, Britain Oct. '7, 1930 thiourea.

BRUCE EARLE BAKER. OTHER REFERENCES LEO BRICKMAN Wmnek et a1: Jour. Am.Chem. 800., vol. 64

EDWARD N (1942), p. 1682.

1. IN A PROCESS FOR THE PREPARATION OF SULFANILYLTHIOUSREAS ANDDERIVATIVES, THE STEPS COMPRISING HEATING AN AQUEOUS SUSPENSION OFCALCIUM ACETYL SULFANILYLCYANAMIDE AT A TEMPERATURE OF AT LEAST 70* C.WITH HYDROGEN SULFIDE UNDER PRESSURE, AND THEREAFTER DISSOLVING SODIUMCHLORIDE INTO THE AQUEOUS REACTION MIXTURE AND CRYSTALLIZING OUT THESODIUM SALT OF ACETYL SULFANILYLTHIOUREA FROM THE AQUEOUS REACTIONMIXTURE.